Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether cetuximab is more effective when given alone or together with sorafenib tosylate in treating patients with head and neck cancer. This randomized phase II trial is studying cetuximab to see how well it works when given together with or without sorafenib tosylate in treating patients with refractory, recurrent, and/or metastatic head and neck cancer

Phase II Randomized Trial of the Combination of Cetuximab and Sorafenib or Single Agent Cetuximab in Patients With Refractory, Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Progression free survival (PFS) [ Time Frame: From study entry to disease progression or death, whichever is earlier, assessed up to 3 years ] [ Designated as safety issue: No ]

Will be summarized with the Kaplan-Meier curve by arm. Confidence intervals for the median and survival rates at different time points will be constructed when appropriate.

Secondary Outcome Measures:

Response rate (CR+PR) [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]

Will be summarized using both point estimates and exact confidence intervals based on the binomial distribution by arm. The Fisher exact/Chi-square test and logistics regression will be considered to study the relationship between various disease or patient characteristics/ gene expression/ proteomic groups and response by arm and/or overall.

Overall survival [ Time Frame: From study entry to death of any causes, assessed up to 3 years ] [ Designated as safety issue: No ]

Will be summarized with the Kaplan-Meier curve by arm. Confidence intervals for the median and survival rates at different time points will be constructed when appropriate.

Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21.

Biological: cetuximab

Given IV

Other Names:

C225

C225 monoclonal antibody

IMC-C225

MOAB C225

monoclonal antibody C225

Other: placebo

Given orally

Other Name: PLCB

Other: laboratory biomarker analysis

Correlative studies

Procedure: quality-of-life assessment

Ancillary studies

Other Name: quality of life assessment

Experimental: Arm II (cetuximab and sorafenib tosylate)

Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral sorafenib tosylate twice daily on days 1-21.

Biological: cetuximab

Given IV

Other Names:

C225

C225 monoclonal antibody

IMC-C225

MOAB C225

monoclonal antibody C225

Drug: sorafenib tosylate

Given orally

Other Names:

BAY 43-9006

BAY 43-9006 Tosylate Salt

BAY 54-9085

Nexavar

SFN

Other: laboratory biomarker analysis

Correlative studies

Procedure: quality-of-life assessment

Ancillary studies

Other Name: quality of life assessment

Detailed Description:

PRIMARY OBJECTIVES:

I. Compare the progression free survival (PFS) of the combination of cetuximab and sorafenib to that of cetuximab alone in patients with recurrent, refractory or metastatic squamous cell carcinoma of the head and neck (SCCHN).

SECONDARY OBJECTIVES:

I. To evaluate the response rate, overall survival (OS) and toxicity of the combination of cetuximab and sorafenib and of cetuximab alone.

II. To evaluate the presence of EGFRvIII mutation, increased EGFR gene copy number and activated EGFR gene expression signature, and correlate with clinical parameters (RR, OS and PFS) in the cetuximab alone and cetuximab/sorafenib arms.

III. To evaluate whether VEGF receptor family and their ligand expression can predict response to cetuximab/sorafenib.

IV. To determine the proteomic profiles in serum and tumors that can predict the response and survival upon the treatment with cetuximab or cetuximab/sorafenib.

V. To evaluate the effect of therapy on both general and head and neck specific functionality, symptom burden and QOL.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cetuximab IV over 60-120 minutes on days 1, 8, and 15 and oral placebo twice daily on days 1-21. (oral placebo closed as of 02/18/2010).

In both arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Paraffin embedded tissue samples are collected at baseline for pharmacogenomic studies and blood samples are collected at baseline and for the first 3 courses for research purposes. Quality of life and symptom burden are assessed by Vanderbilt Head and Neck Symptom Survey, FACT-HN, and Fatigue and Pain Inventory questionnaires at baseline, at day 43, and at 3 and 6 months.

After completion of study treatment, patients are followed periodically for 3 years.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Patients with recurrent, refractory or metastatic squamous cell carcinoma of oral cavity, oropharynx and larynx, hypopharynx or paranasal sinus, head and neck unknown primary or nasopharyngeal carcinoma WHO type 1; patients with recurrent, refractory or metastatic squamous cell carcinoma of oral cavity, oropharynx and larynx, hypopharynx or paranasal sinus, head and neck unknown primary or nasopharyngeal carcinoma WHO type 1; patients may have had up to 1 prior palliative chemotherapy for recurrent or metastatic disease; please note that chemotherapy given as part of a regimen for curative intent for recurrent disease does not count as "prior chemotherapy;" patients must not presently be candidates for curative therapy

If primary therapy was given for curative intent, at least 4 weeks must have elapsed after completion of primary therapy prior to enrollment on this clinical trial; however, toxicities from prior treatment must have resolved to grade 1 or less

Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of the treatment; women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation (i.e, a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for a minimum of 3 months following the last dose of chemotherapy; male subject agrees to use an acceptable method for contraception for the duration of the study and for a minimum of 3 months following the last dose of chemotherapy

Patients must have a measurable disease defined by RECIST criteria

Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care; patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial

Exclusion Criteria:

Prior treatment with sorafenib or cetuximab

Patients with active clinically significant infection or with a fever >= 38.5º C within 3 days of the first scheduled day of protocol treatment

History of prior malignancy within the past 3 years except for curatively treated basal cell carcinoma and squamous cell carcinoma of the skin, CIN or localized prostate cancer with a current PSA < 1.0 mg/dL on 2 successive evaluations at least 3 months apart, with the most recent evaluation within 4 weeks of study entry

Patients with known hypersensitivity to sorafenib or cetuximab

Prior severe infusion reaction to a monoclonal antibody

History of hand-foot syndrome

Pregnant or lactating; sexually active women of childbearing potential must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized

Known untreated brain metastasis; patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis or progression of brain metastasis; patients with treated brain metastasis are eligible for study as long as no evidence of progression of CNS disease; hemorrhagic brain metastases are not allowed on study

Uncontrolled comorbid illness

Patients with HIV who are taking antiretroviral mediations will be excluded because of the potential interactions of anti-retroviral medications with these agent; however, given the potential immune modulating effects of sorafenib, investigators should still be very cautious about placing HIV positive patients on this trial as the effects of these medications on the HIV virus itself are not know

History of allogeneic transplant

Patient has received other investigational drugs within 28 days before enrollment

Any other hemorrhage/bleeding event > CTCAE grade 3 within 4 weeks of first dose of study drug

Tumor that invades the carotid artery as shown unequivocally by imaging studies

Serious non-healing wound, ulcer, or bone fracture

Evidence or history of bleeding diathesis or coagulopathy

Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug

Use of St. John's Wort or rifampin (rifampicin)

Use of the following medications will not be allowed within 4 weeks prior to enrollment on the study and during the study: ketoconazole, itraconazole, ritonavir, cyclosporine, carbamazepine, phenytoin, phenobarbital; products containing grapefruit juice will not be allowed while on study

Known or suspected allergy to sorafenib or any agent given in the course of this trial

Any malabsorption problem

Known HIV positive patients will be excluded from trial due to the potential immune modulation that these agents may cause

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00939627